J:11381

(DBA/2J x EL)F1 x DBA/2J and (ABP/LeJ x EL)F1 x ABP/LeJ backcross populations were used to map QTLs associated with susceptibility to epileptic seizures. Parental strain EL is highly susceptible to epileptic seizures whereas parental strains DBA/2J and ABP/LeJ are resistant. F1 hybrid animals exhibit seizure susceptibility to a lesser degree than parental strain EL.

A locus with significant association to epileptic seizures, El1, was detected on mouse Chromosome 9 (P<0.001) in both backcross populations. El1 maps near Mpmv27, Myo5a, Bmp5, and Glb1 and gives a peak LOD score of 5.88 between Glb1 and Bmp5. A locus significantly linked to seizures, El2, was detected on mouse Chromosome 2 (P<0.001) in the (ABP/LeJ x EL)F1 x ABP/LeJ backcross population. El2 is linked to Mpmv28 with a peak LOD score of 5.2.

7.13.2015 Curator Note: Because two different crosses were used in this study we consider each QTL to be unique. We have left the QTL identified here, using the (DBA/2J x EL)F1 x DBA/2J backcross, with the original El1 nomenclature. We have named the QTL identified using the (ABP/LeJ x EL)F1 x ABP/LeJ backcross as El7.

J:114157

Previously identified loci (chr 2, 9, and 10) associated with idiopathic generalized epilepsy were examined in (ABP/LeJ x EL/Suz)F2 animals to determine their effect in different environments. Parental strain EL/Suz is susceptible to spontaneous epileptic seizures whereas parental strain ABP/LeJ is non-epileptic. Seizure susceptibility appears to follow dominant inheritance after repeated testing in young or old mice, but appears to follow recessive inheritance in a single test in old mice. Animals were tested under 3 different environments. Environment 1 involved young animals (age 30 days) tested for seizures at four 30-day intervals, with the last test used for genotype analysis. Environment 2 involved old animals (age 150 days) tested once for seizures. Environment 3 involved old animals (age 150 days) tested for seizures at four 30-day intervals, with the last test used for genotype analysis.

Linkage to El4 (epilepsy 4) on mouse Chromosome 9 was detected in Environment 1 near D9Mit22 (LOD=4.35). This locus explained 20.1% of the variance and the QTL interval spanned D9Mit22 (28 cM) to D9Mit32 (35 cM). A novel locus named Elnv (epilepsy nave) was identified between D9Mit188 (9 cM) and D9Mit2 (17 cM) in Environment 2 with LOD=3.46. Elnv explained 9.2% of the variance. El4 and Elnv were also detected in Environment 3 (LOD=4.28 and LOD=6.29, respectively). El4 explained 12.7% of the variance, and Elnv explained 15.7% of the variance in Environment 3. Gria4 (8 cM) is a potential candidate gene for Elnv.

Linkage to El2 (epilepsy 2) on mouse Chromosome 2 was detected in Environment 1, but only in females. El2 mapped between D2Mit30 (69 cM) and D2Mit21 (80 cM) with LOD=3.72, and accounted for 35.2% of the variance.

Suggestive linkage to El3 (epilepsy 3)on mouse Chromosome 10 was detected in Environment 2 (LOD=2.29). El3 mapped between D10Mit42 and D10Mit134, and accounted for 5.6% of the variance.